Mixed Brain Fuel – Q&A

Question: On a ketogenic diet, how rapidly does the brain flip between glucose and ketones for fuel? Can it use both fuel sources simultaneously?

Answer: The above question sort of encompasses a few different potential things and I’m not 100% sure which you’re asking so I’ll just cover them all. First realize that one fuel that the brain cannot use is fatty acids, at least not directly. This has led to the oft-stated belief that the brain can only use glucose. But this is incorrect as the brain has an alternative fat derived fuel which are ketones (or ketone bodies, the two major of which are beta-hydroxybutyrate and acetyl-acetate).

Ketones are produced primarily in the liver (from the breakdown of fatty acids) and exist predominantly as an alternative fuel source for the brain (they can also be used by skeletal muscle) during periods of low-carbohydrate availability. This probably was originally important during periods of complete starvation; now very low-carbohydrate diets (defined here as any diet containing less than 100 grams per day of carbohydrates) effectively ‘exploit’ this mechanism.

Now, on a carbohydrate based diet, the brain runs essentially on 100% glucose since ketones are generally not produced in significant amounts under those conditions (there are a couple of odd exceptions, one is following very long duration endurance exercise where a post-exercise ketosis can occur due to changes in fuel metabolism). So what happens when you remove most or all carbohydrates from the diet? Does the brain magically switch to using ketones? For the most part, no. Studies done way back when show that there is an adaptation phase that may last about 3 weeks while the brain ramps up its ability to use ketones for fuel.

Even there, after that roughly 3 week period, the brain still only derives about 75% of its total fuel requirements (about 400 calories per day or thereabouts) from ketones; the other 25% come from glucose (which the body can produce through a variety of pathways that I won’t detail here; all of this is explained in excruciating detail in my first book The Ketogenic Diet). Mind you, this is only relevant on a very low-carbohydrate diet. Even if the brain could still use ketones on a carb-based diet they wouldn’t be produced in large enough amounts for it to be relevant.

So I think that answers at least part of your question: when first starting a low-carbohydrate diet, it takes the brain about 3 weeks to adapt to using ketones for fuel; even then it only gets about 75% of its total fuel from them. This scans pretty well with what many experience on the diet, they don’t feel fantastic for the first 2-3 weeks of the diet (while they are adapting). Some of that, mind you, is related more to mineral intake than anything else (early studies found that sufficient intake of sodium, potassium and magnesium eliminated all of the fatigue and lethargy that occurred on very low carbohydrate diets).

But there is a related question that often comes up which has to do with switching back and forth between fuels (this is especially relevant for some cyclical ketogenic diets such as what’s described in The Ketogenic Diet or in my Ultimate Diet 2.0). Here I am unaware of any research on the topic and most of what I have to say is just based on empirical evidence, what people have reported over the 15+ years they’ve been giving me feedback.

Certainly early in the diet there is often a period where the alternation of high and low carbs often causes some people distress, they get the same headaches and issues going from high-carbs back to low-carbs for a couple of weeks. Probably just a function of ‘interrupting’ the adaptation to ketone metabolism in the brain and there might be some rationale to doing 2-3 straight weeks of a ketogenic diet prior to inserting refeeds or carb-loads.

At the same time, after more extended periods on the diet (perhaps 6-8 weeks), switching back and forth from a carb-based to a ketone-based brain metabolism seems to cause most people no problems. They can sort of drop in and out of ketosis (even throughout the day under certain conditions) and not really notice anything one way or the other. Interestingly, even after extended periods off of a low-carbohydrate diet, most people don’t report the same early adaptation phase that they went through the first time on the diet; they go back onto a ketogenic diet and don’t notice anything.

This suggests to me that there is some type of long-term and/or almost permanent change in the brain in terms of its ability to use ketones for fuel with long-term exposure to them. Again, I have exactly zero research to back this up; it’s just an observation. But even there you’d still expect to see the same basic 75/25 split, just with an easier switching back to ketone metabolism after that initial adaptation phase.